de Lonlay Pascale, Simon-Carre Aurore, Ribeiro Maria-João, Boddaert Nathalie, Giurgea Irina, Laborde Kathleen, Bellanné-Chantelot Christine, Verkarre Virginie, Polak Michel, Rahier Jacques, Syrota André, Seidenwurm David, Nihoul-Fékété Claire, Robert Jean-Jacques, Brunelle Francis, Jaubert Francis
Département de Pédiatrie, Hôpital Necker-Enfants Malades, Université Paris-Descartes, Faculté de Médecine, 149 rue de Sèvres, 75743 Paris cedex 15, France.
J Clin Endocrinol Metab. 2006 Mar;91(3):933-40. doi: 10.1210/jc.2005-1713. Epub 2006 Jan 10.
Congenital hyperinsulinism (HI) is characterized by hypoglycemia related to inappropriate insulin secretion. Focal and diffuse forms of hyperinsulinism share a similar clinical presentation, but their treatment is dramatically different. Preoperative differential diagnosis was based on pancreatic venous sampling, a technically demanding technique.
Positron emission tomography (PET) after injection of [18F]fluoro-L-DOPA (L-dihydroxyphenylalanine) has been evaluated for the preoperative differentiation between focal and diffuse HI, by imaging uptake of radiotracer and the conversion of [18F]fluoro-L-dopa into dopamine by DOPA decarboxylase. We propose to validate this test by immunohistochemical approach.
Pancreatic surgical specimens of four focal and three diffuse HI were studied, using anti-DOPA decarboxylase and proinsulin antibodies. The effect of an inhibitor of DOPA decarboxylase (carbidopa) on insulin secretion was evaluated in vivo and in cultured INS-1 cells.
Immunohistochemical detection of DOPA decarboxylase showed diffuse staining of Langerhans islets in the whole pancreas in all diffuse cases, in contrast with dense focal staining in all focal cases. Staining of Langerhans islets outside the focal lesion was diffusely but weakly positive. We correlated the localization of DOPA decarboxylase and proinsulin in normal pancreas and in both diffuse and focal HI tissues. The diffuse PET uptake found before treatment in one child with diffuse HI disappeared completely after carbidopa administration, suggesting in vivo that pancreatic cells can take up amine precursors and contain DOPA decarboxylase. The insulin secretion measured in the supernatant was the same whether INS-1 cells were treated by dopamine or Lodosyn or untreated.
We validate PET with as a consistent test to differentiate diffuse and focal HI.
先天性高胰岛素血症（HI）的特征是与不适当胰岛素分泌相关的低血糖。局灶性和弥漫性高胰岛素血症具有相似的临床表现，但其治疗方法却截然不同。术前鉴别诊断基于胰腺静脉采血，这是一项技术要求较高的技术。
注射[18F]氟-L-多巴（L-二羟基苯丙氨酸）后的正电子发射断层扫描（PET）已通过放射性示踪剂摄取成像以及DOPA脱羧酶将[18F]氟-L-多巴转化为多巴胺，用于术前区分局灶性和弥漫性HI。我们建议通过免疫组织化学方法验证该测试。
使用抗DOPA脱羧酶和胰岛素原抗体研究了4例局灶性和3例弥漫性HI的胰腺手术标本。在体内和培养的INS-1细胞中评估了DOPA脱羧酶抑制剂（卡比多巴）对胰岛素分泌的影响。
DOPA脱羧酶的免疫组织化学检测显示，在所有弥漫性病例中，整个胰腺的朗格汉斯胰岛均呈弥漫性染色，而在所有局灶性病例中则呈密集的局灶性染色。局灶性病变外的朗格汉斯胰岛染色呈弥漫性但弱阳性。我们将正常胰腺以及弥漫性和局灶性HI组织中DOPA脱羧酶和胰岛素原的定位进行了关联。一名弥漫性HI患儿在治疗前发现的弥漫性PET摄取在给予卡比多巴后完全消失，这表明在体内胰腺细胞可以摄取胺前体并含有DOPA脱羧酶。无论INS-1细胞是用多巴胺、Lodosyn处理还是未处理，在上清液中测得的胰岛素分泌都是相同的。
我们验证了PET作为区分弥漫性和局灶性HI的一致性测试。
Zotero 插件